Nationwide survey of patients with acute liver failure and late-onset hepatic failure in Japan seen between 2016 and 2021

Aim: A nationwide survey was conducted to clarify the recent status of patients with acute liver failure (ALF) and late-onset fulminant hepatitis (LOHF) in Japan. Methods: Two-step surveys were performed annually targeting 782 hospitals, focusing on patients meeting the Japanese diagnostic criteria. Results: A total of 1404 patients seen between 2016 and 2021 were enrolled, including 1373 patients with ALF (824 non-comatose, 320 acute type, and 229 subacute type) and 31 patients with LOHF. Of these, 1117 patients (79.6%) had hepatitis, and 287 patients (20.4%) did not have hepatitis. Compared to patients seen from 2010 to 2015, those from 2016 to 2021 showed a decrease in the proportion of viral cases across all types compared to those up to 2009, whereas the proportion of drug-induced, autoimmune, and indeterminate cases increased. Among the patients, 32 had HBV reactivation due to immunosuppressive and/or antineoplastic therapies (17 HBsAg positive and 15 HBsAg negative). The frequency of complications and various treatment methods did not show significant changes compared to previous surveys. Excluding non-comatose cases, the survival rate with medical treatment for patients with and without hepatitis remained low. Liver transplantation was performed in 144 patients with hepatitis (12.9%) and in 19 patients without hepatitis (6.6%). Multivariate analysis identified disease types, patient age, etiology, liver atrophy, and complications as factors associated with the outcome. Conclusion: Although the clinical features and etiologies of patients with ALF and LOHF have evolved, patient outcomes have not improved in recent years.